Investigations will be carried out to define the underlying basis for the absence of enzyme activity that occurs in five ganglioside storage diseases: Tay-Sachs disease, Sandhoff's disease, juvenile GM2 gangliosidosis, GM1 gangliosidosis Type I and GM1 gangliosidosis Type II. These investigations will include purification of normal hexosaminidase A and B and B-galactosidases A, B, and C to homogeneity in quantities sufficient for structural studies, and under purification conditions whereby the proteins are obtained in an unaltered state. The procedure for purification which will be relied heavily upon is that of affinity chromatography. Subsequent to the purification of each enzyme, investigations will be carried out to determine whether structurally altered and enzymically inactive proteins are present in the patient's tissue which are immunologically similar to the normal proteins. These investigations should provide a deeper understanding of the normal activity of the enzymes which participate in ganglioside GM1 and ganglioside GM2 catabolism, as well as an appreciation of the molecular basis for deficient enzyme activity at the protein level that occur in ganglioside storage diseases.